September 26, 2012

Kinase Inhibitors Quicken Stem Cell Production Process

Scientists from the La Jolla, California-based Sanford-Burnham Medical Research Institute recently discovered kinase inhibitors, which could help facilitate the production of stem cells in the laboratory as well as increase the amount of cells for projects related to disease research and drug development.

Researchers were initially interested in quickening the process utilized in the production of induced pluripotent stem cells (iPSCs), a special group of stem cells that can be derived from any kind of an adult cell in the laboratory. iPSCs have been used to produce cells of all types, including cells from the brain, heart and muscles.

The team of investigators found that kinase inhibitors could limit the activity of kinase, enzymes that assist in cellular communication, growth and survival. When they combined starter cells along with kinase inhibitors, they discovered that they could produce more iPSCs than the method that has been used in the past by scientists.

"Generating iPSCs depends on the regulation of communication networks within cells," remarked the study´s senior author Tariq Rana, program director in Sanford-Burnham's Children's Health Research Center, in a prepared statement. "So, when you start manipulating which genes are turned on or off in cells to create pluripotent stem cells, you are probably activating a large number of kinases. Since many of these active kinases are likely inhibiting the conversion to iPSCs, it made sense to us that adding inhibitors might lower the barrier."

The scientists focused on identifying kinase inhibitors with a group of over 240 chemical compounds that limited kinase. The compounds were each added to the cell and many of the kinase inhibitors generated more iPSCs than the untreated cells. They found that the more powerful inhibitors focused on kinases AurkA, P38, and PI3K. Team members from Rana´s laboratory collaborated with staff members from Stanford-Burnham´s bioinformatics, animal modeling, genomics and histology core facilities to confirm the findings of the study.

"We found that manipulating the activity of these kinases can substantially increase cellular reprogramming efficiency," continued Rana in the statement. "But what's more, we've also provided new insights into the molecular mechanism of reprogramming and revealed new functions for these kinases. We hope these findings will encourage further efforts to screen for small molecules that might prove useful in iPSC-based therapies."

With this new finding, researchers will be able to create new treatments and examine human disease. For example, researchers can use stem cells in Alzheimer´s disease studies in reproducing malfunctioning brain cells from an individual. These cells can then be observed in therapeutic drug testing.

"The identification of small molecules that improve the efficiency of generating iPSCs is an important step forward in being able to use these cells therapeutically. Tariq Rana's exciting new work has uncovered a class of protein kinase inhibitors that override the normal barriers to efficient iPSC formation, and these inhibitors should prove useful in generating iPSCs from new sources for experimental and ultimately therapeutic purposes," Tony Hunter, a professor in the Molecular and Cell Biology Laboratory at the Salk Institute for Biological Studies and director of the Salk Institute Cancer Center, and unaffiliated with the study, said in the statement.